Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism.

To evaluate coronary flow reserve during cardiac catheterization, intracoronary adenosine and papaverine have been used in the clinical setting. Although papaverine maximizes coronary blood flow, it induces several toxic side effects that reduce its desirability as a coronary dilator. This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model. In dogs (n = 34), we studied the effects of each agent on hemodynamics, regional myocardial blood flow, contractility (sonomicrometric and echocardiographic), metabolism (coronary arterial and venous lactate and tissue high-energy phosphates), and electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine anesthesia/analgesia was induced, and a left thoracotomy was performed. An arterial shunt was created from the left carotid artery to the left anterior descending coronary artery. Two separate groups were studied: group 1 (n = 16) for regional myocardial blood flow and mechanical function and group 2 (n = 18) for biochemical measurements. Adenosine (67 +/- 2 micrograms/min) or papaverine (6 +/- 1 mg/min) was infused into the coronary shunt at a rate of 0.5 + 0.1 ml/min for a maximum duration of 3.5 minutes. Regional myocardial blood flows were determined at control (predrug) and maximal coronary flow using radiolabeled microspheres. All hemodynamic, wall motion, biochemical, and electrocardiographic parameters were also measured at these times. Both drugs produced comparable increases in total and regional coronary blood flows (adenosine, 1.21 +/- 0.15 to 4.83 +/- 0.36 ml/min/g; papaverine, 1.21 +/- 0.05 to 4.89 +/- 0.28 ml/min/g) upon infusion into the left anterior descending coronary artery. Papaverine produced significant (p less than 0.05) changes in subendocardial ST segment electrocardiogram (-2.5 mm), QT prolongation (8 +/- 2%), myocardial creatine phosphate (47% decrease), and coronary sinus serum lactate (277% increase) compared with control. In addition, intracoronary papaverine induced an abnormal contractile pattern. No significant changes in any of these parameters (i.e., ST segment, QT prolongation, myocardial creatine phosphate level, or lactate level) were observed with intracoronary adenosine infusions. We conclude that intracoronary adenosine is comparable to papaverine for maximizing coronary blood flow without the deleterious properties observed with intracoronary papaverine.

Regional myocardial blood flow with a reperfusion catheter and an autoperfusion balloon catheter during total coronary occlusion.

We investigated the ability of two new coronary perfusion catheters to maintain regional myocardial blood flow throughout a 90-minute period of occlusion. In 21 dogs (group I = total occlusion control; group II = reperfusion catheter; group III = autoperfusion balloon catheter) we studied regional blood flow, distal coronary perfusion pressure, infarct size, and red blood cell hemolysis after placement of either catheter into the left anterior descending coronary artery. Regional (microsphere) blood flow showed a reduction in transmural blood flow during occlusion in comparison to baseline values (1.07 +/- 0.12 to 0.81 +/- 0.11 and 1.01 +/- 0.16 to 0.73 +/- 0.08 ml/min subendocardial perfusion for groups II and III, respectively). Comparable changes in blood flow were observed in the subepicardial and midmyocardial regions. Distal coronary perfusion pressures were reduced by 26% and 28% for groups II and III, respectively. Both catheters prevented significant infarction and maintained adequate regional myocardial blood flow throughout the 90-minute period of occlusion without significant complications of clotting or destruction of erythrocytes.

Inadequate subendocardial oxygen delivery during perfluorocarbon perfusion in a canine model of ischemia.

Perfusion of the coronary artery distal to an occlusion was performed in 16 canine preparations to compare the mechanical perfusion of autologous blood to the perfluorocarbon fluosol DA, 20% emulsion (FDA-20). Both substances were perfused under similar conditions (30, 60, and 80 ml/min) and regional electrograms, contractility, and coronary perfusion were measured relative to native coronary perfusion. Autologous blood (60 and 80 ml/min) produced a significant increase in regional (epicardial, midmyocardial, and endocardial) and transmural flow, but not in the endocardial/epicardial perfusion ratio. No other significant changes were observed during autologous blood perfusion. In contrast, FDA-20 perfusion resulted in significant ST depression (-1.8 +/- 0.2, -1.7 +/- 0.2, and -1.3 +/- 0.3 mm) at 30, 60, and 80 ml/min, respectively. FDA-20 also induced a significant decrease in distal diastolic coronary pressure and resistance, a significant decrease in the endocardial/epicardial perfusion ratio at all three perfusion rates, and a significant reduction in delivery of O2 to the subendocardium. These results indicate that autologous blood perfusion of the distal coronary artery during occlusion preserves myocardial function to a better degree than does FDA-20.